Lung cancer in older patients with granulomatosis with polyangiitis: a report of three cases.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterized by necrotizing granulomatous inflammation with necrotizing vasculitis predominantly affecting small to medium vessels. The survival rates have drastically improved; however, GPA can be lethal, with older patients having a worse prognosis and higher mortality than younger patients. Moreover, the incidence of various cancers has been reported to increase in patients with GPA. We aimed to discuss possible associations between GPA and lung cancer and emphasize the associated diagnostic challenges. CASE PRESENTATION: We encountered three older patients with chronic GPA who developed lung cancer during long-term follow-up. Two of the patients had a smoking history, with one having silicosis and the other having chronic obstructive pulmonary disease. Furthermore, all of them had radiation exposure from repeated radiography/computed tomography. All the patients had confirmed GPA, and vasculitis relapse was first suspected when new lung lesions were noted during follow-up. However, they had no new clinical symptoms, and serum ANCA titer increased only in one patient. All the patients received standard immunosuppressive treatment but eventually died. CONCLUSIONS: Lung cancer is uncommon in patients with GPA; however, the similarity between the imaging findings of lung cancer and GPA may pose a diagnostic challenge. Clinicians should be particularly vigilant when treating older patients with an increased risk of cancer, as they are often asymptomatic or have poorly apparent clinical features.

Evaluation of prognostic factors for patients with eosinophilic granulomatosis with polyangiitis recruited at the pneumonological centre and mainly ANCA negativity: A retrospective analysis of a single cohort in Poland.

OBJECTIVES: The aim was to investigate the risk factors for relapse and death in patients with eosinophilic granulomatosis with polyangiitis (EGPA) recruited at the pneumonological centre and mainly antineutrophil cytoplasmic antibody negativity. METHODS: We retrospectively recruited 86 patients. Relapse was defined as the recurrence or appearance of new organ symptoms. The study end-point included the final examination. RESULTS: Relapses occurred in 34.9% of the patients, while 9.3% died. Immunosuppressive therapy (P = 0.042), prolonged low-dose corticosteroid treatments (mainly for asthma) (P = 0.006), and longer follow-up duration (P = 0.004) were associated with a higher relapse risk, while advanced EGPA severity (P = 0.0015) and activity (P = 0.044), older age of onset (P = 0.030), symptomatic cardiac involvement (P = 0.007), and postinflammatory cardiac fibrosis (P = 0.038) were associated with a higher risk of death. Sinusitis (P = 0.028) and prolonged low-dose corticosteroid treatments (P = 0.025) correlated with a better prognosis. Relapses did not have an impact on the mortality (P = 0.693). CONCLUSIONS: Relapses in EGPA remain frequent, although they do not impact mortality. Cardiac involvement is common, but clinically symptomatic cardiomyopathy is associated with a higher risk of death. Asthma requiring chronic corticosteroid treatments is associated with a lower risk of death, although the risk of EGPA recurrence is significantly higher.

Antineutrophil cytoplasmic antibodies (ANCA) - their role in pathogenesis, diagnosis, and treatment monitoring of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCA. Increasing clinical and experimental evidences support their pathogenic role in AAV, but the exact mechanism is not fully understood. Recently, the important role of neutrophil extracellular traps (NETs) in pathogenesis of AAV is underlined. There is an indication that NETs can be a source for the formation of ANCA. The most common ANCA target antigens are myeloperoxidase (MPO) and proteinase 3 (PR3). Though the mechanism of action of ANCA is still under exploration, ANCA serology is being increasingly used for classification of AAV and revealed as kenner in defining various disease subsets associated with different genetic background, clinical features, treatment response, and prognosis. Controversy exists regarding the utility of serial measurements of ANCA in patients with AAV to monitor treatment and predict disease relapse.

The presence of staphylococcal superantigens in nasal swabs and correlation with activity of granulomatosis with polyangiitis in own material.

OBJECTIVES: Nasal carriage of Staphylococcus aureus and its superantigens (SAg) seem to be a risk factor disease exacerbation in granulomatosis with polyangiitis (GPA). We investigated the association between the presence of SAg in nasal swabs and activity of disease in GPA patients also taking into account correlation with an antimicrobial treatment. METHODS: In a prospective study of a total of 150 GPA patients hospitalised in the period 2009-2016, nasal swabs were examined for the presence of Staphylococcus aureus and SAg. Subsequently, the association with disease activity was assessed. RESULTS: Of 362 Staphylococcus aureus-positive nasal swab cultures from 115 of the 150 patients, the presence of at least one SAg in 126 samples (34.8%) from 56 patients (48.7%) was found. Among the 17 patients with limited to subglottic stenosis (SGS) disease, SAg were detected in 6 cases (35.3%). We did not find a significant correlation between the presence of SAg and disease activity (p=0.986), although when individual SAg were analysed separatively, SED and TSST-1 were more frequently present in active disease. Additionally, the results of the analysis demonstrated a protective effect of trimethoprim/sulfamethoxazole (T/S) treatment (0R 0.52, p<0.0092) in GPA patients. Interestingly, GPA limited to SGS appeared as an unfavourable factor associated with disease activity (0R 1.84, p=0.05). CONCLUSIONS: The association between staphylococcal SAg in nasal swabs and GPA activity is not evident. Multiple mechanisms that may lead to disease activation still need to be investigated.

Atypical image of pulmonary alveolar proteinosis - a case report.

Pulmonary alveolar proteinosis is a very rare interstitial lung disease caused by abnormal intra-alveolar surfactant accumulation. Usually, it appears as a "crazy-paving" pattern on high-resolution computed tomography. The image is so typical, that together with the characteristic bronchoalveolar lavage examination with presence of Periodic Acid Schiff positive substance is sufficient for establishing diagnosis, without histological confirmation. We present the case of the young woman with severe dyspnoea suspected of acute hypersensitivity pneumonia. The computed tomography showed numerous intralobular nodules uniformly distributed troughout the lungs. Treatment by corticosteroids had no clinical effect and next computed tomography showed progression. Despite the high risk of complications (patient had a respiratory failure), a surgical lung biopsy was performed and the histopathological diagnosis of pulmonary alveolar proteinosis was made. The whole lung lavage procedure performed twice caused regression of radiological lesions and respiratory failure.

Pulmonary alveolar proteinosis during a 30-year observation. Diagnosis and treatment.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by the abnormal accumulation of surfactant-like material in macrophages within the alveolar spaces and distal bronchioles. The course of the disease is variable and the prognosis is often good. However, progressive disease in some patients can cause respiratory dysfunction and can be life threatening. In this situation, the only effective treatment is whole lung lavage. The objective of the study was to present the characteristics and the course of pulmonary alveolar proteinosis in our own material, the diagnostic methods used, the indications for treatment and the treatment efficacy. MATERIAL AND METHODS: Retrospective analysis included 17 patients: 6 women and 11 men, aged from 32 to 56 years, who were observed in the Third Lung Department of Pneumonology at the National Institute of Tuberculosis and Lung Diseases between 1984 and 2013. In all patients chest X-ray, pulmonary function test and blood gases were performed. In 15 patients, high-resolution computed tomography (HRCT) was obtained. Bronchoscopy was performed in all of the patients, and in 7/17, bronchoalveolar lavage (BAL) was carried out. Fourteen patients underwent open lung biopsy. The indications for whole lung lavage (WLL) were progression of dyspnoea with restriction of daily activity and/or hypoxaemia. RESULTS: In most of the patients (13/17) the diagnosis was established outside our institute. Patients were referred to our department to establish further procedures. The criteria of diagnosis of PAP in most patients (16/17) was the histological examination of lung tissue, obtained by open lung biopsy (14 cases) and transbronchial lung biopsy (TBLB) (2 cases). Only in one patient the diagnosis was established on the basis of BAL. HRCT imaging was characteristic of proteinosis in 11/15 patients, and BAL examination in 6/7 patients, in whom BAL was performed. In four patients, who had been exposed to injurious factors for many years, secondary proteinosis was recognised; in other patients, no exposure or no other disease was found, and primary alveolar proteinosis was diagnosed. In one patient granulocyte macrophage colony stimulating factor autoantibody was detected. The majority of patients (10/17) had clinical symptoms at the diagnosis. The most commonly reported was dyspnoea, followed by respiratory tract infections. The most common abnormality (12/17) in pulmonary lung test was a decrease of diffusing capacity of the lung for carbon monoxide (DLCO). Respiratory distress at rest was found in two patients. Patients were observed for the period of 6 months to 19 years. Spontaneous partial remission was observed in 10 out of 13 untreated patients, including one complete remission; in 3 cases stabilisation was found in radiological examinations; and in other 4 patients, whole lung lavagewas used, resulting in clinical improvement with partial resolution of lesions in radiological examinations in 3 patients. In one patient, despite WLL being repeated three times, improvement was not achieved. CONCLUSIONS: Pulmonary alveolar proteinosis is a rare interstitial disease with a mild course in most cases. In 13/17 patients diagnosis was based on histological examination of samples from open lung biopsy. The presented patients were observed in the years 1984-2004, and at that time histologic examination was the main diagnostic method. The most common abnormality in pulmonary function tests was decrease of DLCO. In most cases, spontaneous remission of the disease was observed. In four patients with severe course of PAP, WLL was performed with subjective, functional and radiological improvement in 3 of them.

Incidence of alpha-1 antitrypsin Z and S alleles in patients with granulomatosis with polyangiitis--pilot study.

INTRODUCTION: Inherited alpha-1 antitrypsin (AAT) deficiency is one of the three most common genetic disorders in Caucasians. It considerably increases the risk of progressive obstructive lung diseases, mostly chronic obstructive pulmonary disease. It has also been suggested that AAT deficiency might be instrumental vasculitis associated with the anti-neutrophil cytoplasm antibodies (cANCA) and subsequent lung tissue injury. MATERIAL AND METHODS: We present the results from a pilot study involving 51 patients with granulomatosis with polyangiitis, formerly known as Wegener's granulomatosis (GPA), 43 of whom were cANCA positive. The control group consisted of 658 individuals. AAT blood concentration assessment by nephelometry, phenotyping by isoelectrofocusing and real-time PCR genotyping were performed. RESULTS: Deficiency alleles PI*Z and PI*S were detected in 3 (5.88%) and in 2 patients (3.92%) with GPA, respectively. All of them were cANCA positive. In the controls, PI*Z was observed in 2.8% while PI*S in 1.5% of cases. Accordingly, the increased incidence of main deficiency alleles was demonstrated in GPA, and particularly in cANCA+GPA patients, when compared to the controls. The estimated frequency for PI*Z in GPA, cANCA+GPA patients and controls was, respectively, 29.4/1000, 34.9/1000 and 13.7/1000, whereas for PI*S it was 19.2/1000, 23.2/10,00 and 7.6/1000. However, the observed differences did not reach statistical significance due to the considerable size disproportion between groups. CONSCLUSIONS: We believe that our preliminary data confirm the clinical importance of AAT deficiency in GPA patients and the need to screen for AAT deficiency alleles. The study is on-going.

[Diffuse alveolar hemorrhage as the only manifestation of antiphospholipid syndrome]. / Rozlane krwawienie pecherzykowe jako jedyna manifestacja zespolu antyfosfolipidowego.

The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies and the association of protean clinical manifestations as a result of both venous and arterial thrombosis. While pulmonary embolism (secondary to deep vein thrombosis) is common and well-known disturbance in antiphospholipid syndrome, recently there are growing number of case reports describing nonthrombotic lung pathologies in APS. We present here a young male with antiphospholipid syndrome, whose the only manifestation was diffuse alveolar hemorrhage.

Update on cryptogenic organizing pneumonia.

Cryptogenic organizing pneumonia (COP) is a form of idiopathic interstitial pneumonia that results from the pulmonary reaction to various unidentified injuries. Secondary organizing pneumonia is diagnosed when the triggering factor has been identified; it is mainly caused by infections, toxic substance exposure, drugs, connective tissue diseases, malignancies, autoimmune diseases, bone marrow, or organ transplantation, and radiotherapy. There has been an increase in the number of reports of drug-induced organizing pneumonia (OP). New biological therapies, interferon, monoclonal antibodies, anti-interleukin antibodies, and PD1/PDL-1 inhibitors may induce this specific pulmonary reaction. The classical form of COP is usually subacute and does not manifest as severe disease. Patients maintain sufficient respiratory function, and treatment with steroids is usually effective. Several specific forms of OP (e.g., the cicatricial variant or acute fibrinous type) have distinct clinical and histological features, require higher doses of immunosuppressive drugs, and have a worse prognosis. In the era of administering steroid-sparing therapies for the treatment of interstitial lung diseases, connective tissue dases, and other conditions, it is important to emphasize this type of therapy for patients with COP.

Eosinophilic granulomatosis with polyangiitis - Advances in pathogenesis, diagnosis, and treatment.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by eosinophil-rich granulomatous inflammation and necrotizing vasculitis, pre-dominantly affecting small-to-medium-sized vessels. It is categorized as a primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) but also shares features of hypereosinophilic syndrome (HES); therefore, both vessel inflammation and eosinophilic infiltration are suggested to cause organ damage. This dual nature of the disease causes variable clinical presentation. As a result, careful differentiation from mimicking conditions is needed, especially from HES, given the overlapping clinical, radiologic, and histologic features, and biomarker profile. EGPA also remains a diagnostic challenge, in part because of asthma, which may pre-dominate for years, and often requires chronic corticosteroids (CS), which can mask other disease features. The pathogenesis is still not fully understood, however, the interaction between eosinophils and lymphocytes B and T seems to play an important role. Furthermore, the role of ANCA is not clear, and only up to 40% of patients are ANCA-positive. Moreover, two ANCA-dependent clinically and genetically distinct subgroups have been identified. However, a gold standard test for establishing a diagnosis is not available. In practice, the disease is mainly diagnosed based on the clinical symptoms and results of non-invasive tests. The unmet needs include uniform diagnostic criteria and biomarkers to help distinguish EGPA from HESs. Despite its rarity, notable progress has been made in understanding the disease and in its management. A better understanding of the pathophysiology has provided new insights into the pathogenesis and therapeutic targets, which are reflected in novel biological agents. However, there remains an ongoing reliance on corticosteroid therapy. Therefore, there is a significant need for more effective and better-tolerated steroid-sparing treatment schemes.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

[Yellow nail syndrome in a patient with membranous glomerulonephritis]. / Zespól zóltych paznokci u chorego na bloniaste klebuszkowezapalenie nerek.

Yellow nail syndrome (YNS) is a condition characterized by yellow-green coloration of nails, respiratory manifestations and lymphoedema. This article presents 52-year-old patient with membranous glomerulonephritis, hospitalized at the National Tuberculosis and Lung Diseases Research Institute in Warsaw, because of suspected allergic aspergillosis. Based on clinical and radiological evaluation the diagnosis of YNS was established. Treatment of renal disease did not affect the course of yellow nail syndrome. During the two-year follow-up, despite stable renal parameters we observed the progression of respiratory manifestations (bronchiectasis, pleural effusions).

[The basis of Churg-Strauss syndrome diagnosis in own material]. / Podstawy rozpoznania zespolu Churga-Strauss w materiale wlasnym.

INTRODUCTION: The diagnosis of Churg-Strauss syndrome (CSS) is difficult because pathological criteria are present in minority of patients and in advanced stages. Several centers elaborated criteria which allowed to suspect CSS in patients with asthma, hypereosinophilia and clinical manifestations consistent with systemic vasculitis with or without histologic evidence. The aim of the study is the presentation of the basis of CSS diagnosis in our material. MATERIAL AND METHODS: The analysis included 38 patients. Blood and biochemical analysis, radiological examinations of the chest and sinuses, echocardiography were performed in all patients. In 22/23 patients with cardiac symptoms magnetic resonance of the heart was performed. In two patients mediastinoscopy was performed, in 4--laparotomy. RESULTS: Only in 13/38 patients vasculitis was histologically proven, in the rest the diagnosis was established mainly on clinical ground. In 23 patients the diagnosis was established on the clinical cardiac symptoms--in all of them the cardiac involvement was confirmed by magnetic resonance. In 9 cases skin leasions were cause of further diagnostic procedures, 6 patients presented gastrointestinal symptoms, in 15--paralysis of peroneal nerve was observed, and 1 patient had polyneuropathy and symptoms of central nervous system. CONCLUSIONS: The diagnosis of CSS in our material was established mainly on clinical ground, because histologic material was difficult to obtain (it needs invasive procedures). Only in 13 from 38 patients vasculitis was histologically proven. The presence of asthma, sinusitis associated with peripheral eosinophilia and organ symptoms suggesting a vasculitis could support the diagnosis, without histologic evidence.

Chest Pain of Atypical Cause in a Young Man.

Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis that classically affects the upper respiratory tract, lungs, and kidneys. The involvement of other organs occurs but is less frequent. Clinically overt cardiac involvement is rare. We present a rare case of thoracic pain caused by cardiac involvement in GPA, without any other symptoms. The diagnosis was made using an integral approach, with several complementary imaging modalities, including cardiac histology.

The role of peripheral eosinophilia in diagnosing lung disorders: experience from a single pneumonological center.

BACKGROUND: Eosinophilia is rare but one of the important reasons to refer patients to pneumonological centers. Determining etiology of eosinophilia has practical implications for therapeutic intervention and disease prognosis. The study aimed to determine the role of peripheral eosinophilia in the diagnosis of lung disorders. METHODS: In this retrospective study were included 46 patients diagnosed with peripheral eosinophilia with coexisting respiratory symptoms and/or radiologically detected lung lesions. All patients underwent standard diagnostic procedures, including a detailed clinical history review, physical examination, routine laboratory tests with basal cardiological examinations, and serological tests to detect parasites and allergies. Other procedures carried out depended on the symptoms of each patient. The relation between eosinophil counts in the blood and patients' clinical manifestation was investigated to identify the degree of eosinophilia requiring immediate diagnostic procedures and treatment. Statistical analyses were performed using scientific computation libraries in the Python programming language, SciPy, v. 1.3.1. Briefly, the following tests were used: parametric Kruskal-Wallis H test, an independent t-test, ANOVA, the Shapiro- Wilk test, Fisher's and Chi-squared tests, and the Holm-Bonferroni method. RESULTS: Severe eosinophilia (≥5,000 cells/µl) was associated with extrapulmonary involvement and constitutional symptoms. Skin, heart, and pleural diseases were more frequent in these patients than in patients with mild or moderate eosinophilia (p=0.010, p=0.040, and p=0.007, respectively), and only these patients showed signs of kidney disease (p=0.006). Vasculitis was significantly more frequent in the severe eosinophilia group (p=0.048) than in the other two groups. In patients with moderate eosinophilia (1,500-5,000 cells/µl), extrapulmonary symptoms were less common, although signs of cardiac involvement were confirmed in 44% of subjects. In this group, vasculitis was the most commonly observed disease (42% of cases). Mild eosinophilia (<1,500 cells/µl) was mainly associated with airway disease. In this group, vasculitis and interstitial lung diseases were identified, but most were not typically connected with eosinophilia. CONCLUSIONS: Identification of peripheral eosinophilia may essentially determine diagnostic procedures in patients with lung disorders and may be a useful indicator of disease etiology.

[Pleural sarcoidosis - a report of three cases]. / Sarkoidoza z zajeciem oplucnej - opis trzech przypadków.

Three patients with pleural sarcoidosis are reported. Pleural effusion in two patients and a massive pleural thickening that mimicked a tumour were observed. Histological examination of pleural biopsies revealed sarcoidosis. None of the patients received treatment. No recurrence of the pleural effusion was observed after a year of follow-up and the massive pleural thickening remained stable.

Immunological disturbances in Good's syndrome.

BACKGROUND: Immunodeficiency with a thymoma (Good's syndrome) is a rare condition occurring in patients with adult-onset hypogammaglobulinaemia. CLINICAL REPORT: We describe the case of a 38-yr-old woman with an upper mediastinal mass and inflammatory infiltrations in the lungs. After thymectomy, the patient's condition did not improve. The HRCT scan showed bronchiectasies with parenchymal opacities. As pulmonary infection persisted despite wide spectrum antibiotic therapy, additional tests were performed to diagnose an immunodeficiency. Serum immunoglobulin levels were very low. T cell response to mitogens was normal, but to Staphylococcus aureus Cowan I was impaired. Immunophenotyping of peripheral blood and bone marrow aspirate showed a very low number of B-cell at all the stages of development (CD10+CD19+, CD5+CD20). In peripheral blood 2.5% of CD19+ lymphocytes were found. On the basis of clinical history and immunological analysis, Good's syndrome was recognized. Treatment with intravenous gammaglobulin and antibiotics improved the patient's performance. CONCLUSION: Measurement of serum immunoglobulin concentration is recommended for all patients suspected of thymoma.

Difficulties in recognizing granulomatosis with polyangiitis (GPA) in elderly patients undergoing diagnostic thoracotomy twice - a report of two cases.

Granulomatosis with polyangiitis (GPA) is defined as a necrotizing granulomatous inflammation usually involving the upper and lower respiratory tract with necrotizing vasculitis affecting predominantly small to medium vessels. Because of non-specific symptoms, its radiological presentation, and the diversity of its clinical expression, it is not uncommon to for it to be misdiagnosed, especially in the elderly. Although biopsy and histological examination seem to be essential for GPA diagnosis, their results are sometimes ambiguous and not helpful in making a decision. In this report, we present difficulties in the recognition of GPA in two elderly patients in whom, despite twice performing a diagnostic thoracotomy, GPA was recognized almost 4 and 6 years after the first symptoms.

Antineutrophil cytoplasmic antibodies and their relationship with disease activity and presence of staphylococcal superantigens in nasal swabs in patients having granulomatosis with polyangiitis: results of a study involving 115 patients from a single center.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCAs) are considered a risk factor for granulomatosis with polyangiitis (GPA) exacerbation, especially when staphylococcal superantigens (SAgs) are present in nasal swabs. Their role in monitoring disease activity remains controversial. This study determined the relationship of ANCAs with disease activity and presence of SAgs in GPA patients. METHODS: Among a total of 115 GPA patients hospitalized in the period 2009-2016, we investigated the presence of SAgs and ANCA concentration. Blood samples and nasal swabs were taken at each visit (referred further to as episodes). Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). RESULTS: We analyzed 362 episodes. ANCAs were detected in 215 (59.4%), while SAgs were detected in 126 (34.8%) episodes. We found a significant correlation between the presence of ANCAs and disease activity (p = 0.0032), as well as between their level and GPA severity (r = 0.25363, p = 0.000001). We also determined that an ANCA values ≥ 138 Ru/ml were an indicator of active disease with high specificity and low sensitivity (84.4% and 37.3%, respectively). The relationship between ANCA presence and the presence of SAgs was not confirmed; however, when SAgs were analyzed based on the different types, ANCA levels were found to be significantly higher in the group with SAg type B (p = 0.031). CONCLUSIONS: There was no detectable evidence for the association between ANCA level and the presence of SAgs. Although monitoring ANCA levels as a marker of disease activity may be clinically relevant, GPA management cannot proceed on the basis of ANCA levels alone. Key Points • ANCA concentration usually correlates with GPA activity, although in half of patients, ANCAs persist despite effective treatment and clinical remission. • ANCA values of 138 Ru/ml seem to be an indicator of active disease with high specificity, but low sensitivity. • Although there is a relevance for ANCA monitoring as a marker of disease activity, GPA management cannot be based on ANCA levels alone. • The suspected clinical correlation between ANCA formation and SAg presence in nasal swabs is not obvious and requires further investigations.

[Chronic granulomatous disease recognised in 42-years-old patient]. / Przewlekla choroba ziarniniakowa wykryta u 42-letniej chorej.

Chronic granulomatous disease (CGD) comprises a heterogeneous group of diseases that are caused by defect in the superoxide-producing NADPH oxidase of neutrophils. This defect impairs the intracellular killing of microorganisms. Typical manifestations are recurrent bacterial or mycotic infections affecting the lungs, skin, lymph nodes and gastrointestinal tract (liver). Chronic granulomatous disease could be diagnosed on the basis of the anamnesis, clinical picture and results of granulocyte function tests showing impaired phagocytic activity (NBT tests, RDH test and a deficit of superoxide production). Typically symptoms of disease occur in the first years of live, leading often to death in the 2. or 3. decade. Below we present a patient, in whom diagnosis of the CGD was established at the age of 42.